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Volume 104, Issue 1
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Katsunori TOMIYAMA, Noriaki KOSHIKAWA, Masafumi KOBAYASHI1994 Volume 104 Issue 1 Pages 1-5
Published: 1994
Released on J-STAGE: February 06, 2007
JOURNAL FREE ACCESSIn behavioral studies, seeking the regional site of action of centrally acting drugs, injections are normally made directly into a restricted area of the brain using a microsyringe inserted in a guide cannula that had been implanted previously. This paper describes conventional methods for injecting a drug into the rat brain. The common technique used in brain dialysis studies is to apply the drugs focally into the brain by infusing them through the dialysis probe. One of the main problems of this technique is the difficulty in estimating actual doses of the drugs administered. The present paper also describes a microdialysis probe in combination with a microinjection tube to examine changes in the release and metabolism of dopamine within the area where the drugs were injected under experimental conditions similar to those used in behavioral studies. Using this method, we demonstrated the characteristic difference between two benzamide D2-receptor antagonists YM-09151-2 and l-sulpiride on dopamine release in rat striatum.View full abstractDownload PDF (9936K) -
Mamoru HATA1994 Volume 104 Issue 1 Pages 7-18
Published: 1994
Released on J-STAGE: February 06, 2007
JOURNAL FREE ACCESSEffects of maternal exposure to a single and small dose of kainic acid (KA) on the functional development of the offspring were studied in the rat. A single dose of KA at 3 mg/kg or distilled water (DW) was injected on one day during days 11-14 (G11KA-G14KA, G11DW-G14DW) or 17-19 (G17KA-G19KA, G17DW-G19DW) of gestation. The body growth of G14KA-G18KA was significantly larger than that of the controls. In an openfield, alterations observed in the KA-exposed rats were 1) a reduction of the latent time to the first line crossing at 15 days of age, 2) a decrease in ambulation score at 17 days of age and 3) early appearance of rearing behavior at 15 days of age. Frequencies of spontaneous head shakes, grooming and urination during the openfield test were in the normal range. The frequency of 9 mg/kg KA-induced wet-dog shakes increased only in the G17KA male rats when tested in the 5-week-old G12KA, G14KA and G17KA groups. The results indicated that prenatal exposure to a single dose of KA affects the body growth and behavioral development during the infantile period in rats. The alterations in the growth and behavior appear to correlate with the exposure time to KA, days 13-18 of fetal life, which is the principal time of neurogenesis in the hippocampus, cerebral cortex and hypothalamus.View full abstractDownload PDF (19633K) -
Yuko FUJISHIMA, Hideaki HARA, Masamitsu SHIMAZAWA, Koichi YOKOTA, Taka ...1994 Volume 104 Issue 1 Pages 19-29
Published: 1994
Released on J-STAGE: February 06, 2007
JOURNAL FREE ACCESSThe effects of KB-2796, a new Ca2+-channel blocker, on 5-hydroxytryptamine (5-HT)-induced responses were investigated in comparison with those of other Ca2+-channel blockers such as verapamil, flunarizine, diltiazem and nimodipine. In rat cortical membrane, KB-2796 inhibited specific [3H] spiperone binding to 5-HT2 receptors in a competitive manner (Ki = 0.57 μM), but exhibited negligible affinity for radioligand binding to other 5-HT receptor subtypes such as 5-HT1, 5-HT1A, 5-HT1B, 5-HT1C and 5-HT3 at a concentration of 10 or 100 μM. KB-2796 inhibited both 5-HT-stimulated shape change and 5-HT and collagen-stimulated aggregation in rabbit platelet-rich plasma with IC50 values of 13.4 μM and 96.4 μM, respectively. KB-2796 also inhibited the 5-HT-induced increase of [Ca2+]i, in washed rabbit platelets with the IC50 value of 25.7 μM. Furthermore, KB-2796 (3-30 mg/kg, p.o.) dose-dependently inhibited the 5-HT-induced paw edema in rats. In these experiments, the inhibitory effects of KB-2796 and other Ca2+ channel blockers were related to their affinities for the 5-HT2 receptor; and the potency of KB-2796 was stronger than those of diltiazem and nimodipine and almost equal to that of flunarizine, although all these inhibitors had weaker potencies than that of verapamil. These findings indicate that KB-2796 may possess antagonistic effect on the 5-HT2 receptor.View full abstractDownload PDF (20691K) -
Masami SATO, Yukio KATSUKI, Hideo KANEHIRO, Hiroyuki KAWANO, Masahiro ...1994 Volume 104 Issue 1 Pages 31-38
Published: 1994
Released on J-STAGE: February 06, 2007
JOURNAL FREE ACCESSWe studied the elasticity and endothelium-dependent relaxation (EDR) of the aorta in 1% cholesterol diet (HCD)-fed rabbits. Furthermore, the effects of ethyl all-cis-5, 8, 11, 14, 17-icosapentaenoate (EPA-E) were examined in this model of atherosclerosis. After 12 weeks of feeding with HCD, the animals showed increase in plasma total cholesterol level, formation of atherosclerotic plaque, decrease in aortic elasticity and impairment of EDR to acetylcholine (ACh). The levels of aortic elasticity in HCD-fed rabbits administered orally with EPA-E (300 mg/kg for 12 weeks) were almost the same as those of rabbits fed a normal diet, although EPA-E showed no effects on the plasma total cholesterol level and formation of atherosclerotic plaque in HCD-fed rabbits. On EDR in response to ACh and cyclic GMP formation in the HCD-fed rabbit aorta, EPA-E improved the impairment of these parameters, but not significantly. Therefore, EPA-E had little effect on the endothelium in this model of atherosclerosis, although EPA-E improved the decrease in the aortic elasticity. Because the levels of aortic elasticity showed no significant correlation with the magnitude of EDR to ACh or the size of atherosclerotic plaque, the decrease of aortic elasticity in this model of atherosclerosis was thought to have little relation to the dysfunction of the endothelium.View full abstractDownload PDF (16260K) -
Shigeru MORIMOTO, Go KITO1994 Volume 104 Issue 1 Pages 39-49
Published: 1994
Released on J-STAGE: February 06, 2007
JOURNAL FREE ACCESSThe possibilities of applying the rotarod method in young rats for evaluating the antidepressive effect were studied. The results were compared with those obtained by the despair test, which was also used to evaluate the antidepressive effect. The rats used in these tests had not been trained previously. In the rotarod test, antidepressant drugs such as imipramine (30 mg/kg, p.o.), desipramine (10 mg/kg, p.o.), clorgyline (10 mg/kg, p.o.), mianserin (30 mg/kg, p.o.), trazodone (10 mg/kg, p.o.) and clomipramine (30 mg/kg, p.o.) and an ACE inhibitor, enalapril (30 mg/kg, p.o.), significantly prolonged the time rats were able to remain on the rotating rod in a dose-dependent manner. Diazepam significantly reduced the duration on the rotating rod. Theophylline, caffeine and fenfluramine did not affect the duration on the rotating rod. In the despair test (forced swimming test), clorgyline, enalapril and caffeine significantly reduced the duration of immobility during the forced swimming in a dose-dependent manner. Imipramine and desipramine significantly reduced the duration of immobility during forced swimming. Trazodone and clomipramine did not affect the duration of immobility. Diazepam significantly prolonged the duration of immobility. A highly significant correlation was noted between the results obtained by the rotarod method and those obtained by the despair test. In the traction test, theophylline and caffeine significantly prolonged the duration during the traction response. However, other drugs did not affect the duration during the traction response. These results demonstrate that the rotarod method in young rats may be applicable for evaluating the antidepressive effect.View full abstractDownload PDF (18363K) -
Inhibition of various tissue ACEs ex vivo.Yoshikatsu HASHIMOTO, Masami KUBO, Takeshi SUGAYA, Satoshi MINOBE, Tai ...1994 Volume 104 Issue 1 Pages 51-61
Published: 1994
Released on J-STAGE: February 06, 2007
JOURNAL FREE ACCESSThe antihypertensive mechanism of imidapril was investigated in relation to its inhibition of ACE activities in the serum, thoracic-abdominal aorta, lung, kidney, heart and brain from adult spontaneously hypertensive rats (SHRs). In comparison with normotensive rats (NTRs), the ACE activities in the aorta, heart, brain and lung were higher, while those in the serum and kidney were considerably lower. Imidapril (2 mg/kg) showed remarkable inhibitions within 6 hr in all tissues, except for the brain, after a single oral administration. Consecutive administration of imidapril (2 mg/kg/day) for 30 days produced inhibitions in all tissues. The inhibitions in the serum, aorta and lung were greater, and the duration of inhibition in the aorta, brain and lung were longer. Blood pressure declined gradually until 6 hr, and the reductions were significant at 24 hr after the single and chronic administrations. Imidapril (0.5 mg/kg, ineffective on normal blood pressure) inhibited ACE activities in NTRs similarly. Enalapril at the same dose exhibited less ACE inhibition and antihypertension. These results suggest that the ACE inhibition in the serum, lung and aorta by imidapril correlate with the antihypertension in SHRs; especially, the lung and vascular ACE inhibitions play an important role in the duration of antihypertension in SHRs.View full abstractDownload PDF (21072K)
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